Ultrasound scanners are routinely used in a number of medical applications. A typical example is in diagnostic applications. In this case, ultrasound waves are applied to a body-part of a patient to be analyzed; corresponding echo signals that are recorded in response thereto may be used to create anatomical images (providing a morphological representation of the body-part) or parametric images (providing a spatial distribution of characteristic parameters of the body-part). More recently, the ultrasound scanners have also been introduced in therapeutic applications. In this case, the ultrasound waves are applied to the body-part so as to induce biological effects thereon deliberately; particularly, it is possible to obtain reversible cellular effects (for example, by acoustic (micro) streaming), or cellular death (for example, by indirect effects of (inertial) acoustic cavitation). Typical examples of these therapeutic applications are sonoporation, sonothrombolysis and high intensity focused ultrasound (HIFU) therapy.
The ultrasound scanners may also involve the use of an (ultrasound) contrast agent (UCA), for example, made of a suspension of phospholipid-stabilized gas-filled microbubbles. Particularly, in the diagnostic applications, the reflective characteristics of particles (for example, microbubbles) of the contrast agent facilitate its tracking (for example, to obtain blood perfusion information since the contrast agent flows at the same velocity as red-blood cells in the patient). Moreover, in the therapeutic applications, the contrast agent particles may act as micro-streaming promoters or cavitation nuclei.
A level of acoustic pressure applied to the contrast agent particles by the ultrasound waves largely varies according to the different medical applications. For example, in the diagnostic applications the acoustic pressure should be relatively low to avoid any undesired biological effect on the body-part that might be induced by thermal or non-thermal mechanisms. Conversely, relatively high acoustic pressures are required in the therapeutic applications to achieve the desired effects. For example, acoustic streaming is known to exist when the contrast agent particles oscillate in a stable and reversible way, whereas, in conditions of acoustic cavitation, the contrast agent particles oscillate more violently, eventually leading to their destruction.
The determination of the acoustic pressure that is actually applied in-situ to the contrast agent is relatively simple in in-vitro conditions (wherein it may be measured directly). However, this is very difficult (or even impossible) in in-vivo conditions. Indeed, in this case the acoustic pressure may not be measured in the body-part and it may normally only be estimated from the acoustic pressure of the ultrasound waves that are provided by the ultrasound scanner. However, anatomical structures of the patient interposed between a transducer of the ultrasound scanner and the body-part strongly interfere with the transmission of the ultrasound waves. As a result, the ultrasound waves are subject to attenuation, with a progressive reduction of their acoustic pressure, and thus of energy, during propagation through the anatomical structures. The main source of attenuation of the ultrasound waves (in addition to a minor reflection/scattering thereof) is their absorption by the anatomical structures, wherein the energy of the ultrasound waves is converted to heat (and it is then lost). Moreover, the presence of the contrast agent may also dramatically affect the attenuation of the ultrasound waves. Particularly (in addition to attenuating the energy of the ultrasound waves linearly according to its concentration), the contrast agent has non-linear characteristics that involve a strong dependence of the attenuation of the ultrasound waves on their energy and frequency.
As a consequence, it is not possible to accurately control the acoustic pressure that is actually applied in-situ to the contrast agent particles or to their surroundings. This may hinder several medical applications of the ultrasound scanners in practice. Particularly, the difficulty of controlling the acoustic pressure is detrimental to several therapeutic applications (for example, when a stable and reversible oscillation of the contrast agent particles is required, such as in sonothrombolysis); indeed, since the acoustic pressure that is applied to the contrast agent particles determines their oscillation, the lack of an accurate knowledge thereof may reduce the efficiency of the therapeutic applications (when too low) or it may cause undesired side effects due to an overexposure to the ultrasound waves (when too high).